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ML models were derived in a retrospective cohort of 21,452 ED patients who visited one of five ED study sites and were prospectively validated in 15,670 ED visits that occurred before (<jats:italic>n<\/jats:italic>\u2009=\u20094322) or after (<jats:italic>n<\/jats:italic>\u2009=\u200911,348) CDS implementation; model performance and numerous patient-oriented outcomes including in-hospital mortality were measured across study periods. Incidence of critical care needs within 24\u2009h and inpatient care needs within 72\u2009h were 10.7% and 22.5%, respectively and were similar across study periods. ML model performance was excellent under all conditions, with AUC ranging from 0.85 to 0.91 for prediction of critical care needs and 0.80\u20130.90 for inpatient care needs. 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